The correct oviductal development and morphogenesis of its epithelium are crucial factors influencing female fertility. Oviduct is involved in maintaining an optimal environment for gametes and preimplantation embryo development; secretory oviductal epithelial cells (OECs) synthesize components of oviductal fluid. Oviductal epithelium also participates in sperm binding and its hyperactivation. For better understanding of the genetic bases that underlay porcine oviductal development, OECs were isolated from porcine oviducts and established long-term primary culture. A microarray approach was utilized to determine the differentially expressed genes during specific time periods. Cells were harvested on day 7, 15 and 30 of in vitro primary culture and their RNA was isolated. Gene expression was analyzed and statistical analysis was performed. 48 differentially expressed genes belonging to “tube morphogenesis”, “tube development”, “morphogenesis of an epithelium”, “morphogenesis of branching structure” and “morphogenesis of branching epithelium” GO BP terms were selected, of which 10 most upregulated include BMP4, ARG1, SLIT2, FGFR1, DAB2, TNC, EPAS1, HHEX, ITGB3 and LOX. The results help to shed light on the porcine oviductal development and its epithelial morphogenesis, and show that after long-term culture the OECs still proliferate and maintain their tube forming properties.
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1. Kobayashi A Shawlot W Kania A Behringer RR. Requirement of Lim1 for female reproductive tract development. Development. 2004;131(3):539-49; DOI:10.1242/dev.00951.
2. Massé J Watrin T Laurent A Deschamps S Guerrier D Pellerin I. The developing female genital tract: from genetics to epigenetics. Int J Dev Biol. 2009;53(2-3):411-24; DOI:10.1387/ijdb.082680jm.
3. Yin Y Ma L. Development of the Mammalian Female Reproductive Tract. J Biochem. 2005;137(6):677-83; DOI:10.1093/jb/mvi087.
4. Mullen RD Behringer RR. Molecular genetics of Müllerian duct formation regression and differentiation. Sex Dev. 2014;8(5):281-96; DOI:10.1159/000364935.
5. Kurita T. Normal and Abnormal Epithelial Differentiation in the Female Reproductive Tract. Differentiation. 2011;82(3):117-26; DOI:10.1016/j.diff.2011.04.008.
6. Bernascone I Hachimi M Martin-Belmonte F. Signaling Networks in Epithelial Tube Formation. Cold Spring Harb Perspect Biol. 2017;9(12):a027946; DOI:10.1101/cshperspect.a027946.
7. Leese HJ. The formation and function of oviduct fluid. J Reprod Fertil. 1988;82(2):843-56; DOI:10.1530/jrf.0.0820843.
8. Mondéjar I Acuña OS Izquierdo-Rico MJ Coy P Avilés M. The Oviduct: Functional Genomic and Proteomic Approach. Reprod Domest Anim. 2012;47(3):22-9; DOI:10.1111/j.1439-0531.2012.02027.x.
9. Li S Winuthayanon W. Oviduct: roles in fertilization and early embryo development. J Endocrinol. 2017;232(1):R1-R26; DOI:10.1530/JOE-16-0302.
10. Abe H Hoshi H. Morphometric and ultrastructural changes in ciliated cells of the oviductal epithelium in prolific Chinese Meishan and Large White pigs during the oestrous cycle. Reprod Domest Anim. 2008;43(1):66-73; DOI:10.1111/j.1439-0531.2007.00856.x.
11. White KL Hehnke K Rickords LF Southern LL Thompson DL Jr Wood TC. Early embryonic development in vitro by coculture with oviductal epithelial cells in pigs. Biol Reprod. 1989;41(3):425-30.
12. Kessler M Hoffmann K Brinkmann V Thieck O Jackisch S Toelle B Berger H Mollenkopf HJ Mangler M Sehouli J Fotopoulou C Meyer TF. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun. 2015;6:8989; DOI:10.1038/ncomms9989.
13. Pollard JW Plante C King WA Hansen PJ Betteridge KJ Suarez SS. Fertilizing capacity of bovine sperm may be maintained by binding of oviductal epithelial cells. Biol Reprod. 1991;44(1):102-7.
14. Ren D Navarro B Perez G Jackson AC Hsu S Shi Q Tilly JL Clapham DE. A sperm ion channel required for sperm motility and male fertility. Nature. 2001;413(6856):603-9; DOI:10.1038/35098027.
15. Nagai T Funahashi H Yoshioka K Kikuchi K. Up date of in vitro production of porcine embryos. Front Biosci. 2006;11:2565-73; DOI:10.2741/1991.
16. Huang DW Sherman BT Tan Q Kir J Liu D Bryant D Guo Y Stephens R Baseler MW Lane HC Lempicki RA. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007;35:W169-W175; DOI: 10.1093/nar/gkm415.
17. Walter W Sánchez-Cabo F Ricote M. GOplot: an R package for visually combining expression data with functional analysis. Bioinformatics. 2015;31(17):2912-4; DOI:10.1093/bioinformatics/btv300.
18. von Mering C Jensen LJ Snel B Hooper SD Krupp M Foglierini M Jouffre N Huynen MA Bork P. STRING: known and predicted protein-protein associations integrated and transferred across organisms. Nucleic Acids Res. 2005;33:D433-7; DOI:10.1093/nar/gki005.
19. Chen D Zhao M Mundy GR. Bone Morphogenetic Proteins. Growth Factors. 2004;22(4):233-41; DOI:10.1080/08977190412331279890.
20. Lochab AK Extavour CG. Bone Morphogenetic Protein (BMP) signaling in animal reproductive system development and function. Dev Biol. 2017;427(2):258-269; DOI: 10.1016/j.ydbio.2017.03.002.
21. Erickson GF Fuqua L Shimasaki S. Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle. J Endocrinol. 2004;182(2):203-17.
22. von Schalburg KR McCarthy SP Rise ML Hutson JC Davidson WS Koop BF. Expression of morphogenic genes in mature ovarian and testicular tissues: potential stem-cell niche markers and patterning factors. Mol Reeprod Dev. 2006;73(2):142-52.
23. Abir R Ben-Haroush A Melamed N Felz C Krissi H Fisch B. Expression of bone morphogenetic proteins 4 and 7 and their receptors IA IB and II in human ovaries from fetuses and adults. Fertil Steril. 2008;89(5):1430-40; DOI: 10.1016/j.fertnstert.2007.04.064.
24. Tanwar PS McFarlane JR. Dynamic expression of bone morphogenetic protein 4 in reproductive organs of female mice. Reproduction. 2011;142(4):573-9; DOI:10.1530/REP-10-0299.
25. Böttcher RT Niehrs C. Fibroblast growth factor signaling during early vertebrate development. Endocr Rev. 2005;26(1):63-77; DOI:10.1210/er.2003-0040.
26. Deng C Bedford M Li C Xu X Yang X Dunmore J Leder P. Fibroblast Growth Factor Receptor-1 (FGFR-1) Is Essential for Normal Neural Tube and Limb Development. Dev Biol. 1997;185(1):42-54; DOI: 10.1006/dbio.1997.8553.
27. Pond AC Bin X Batts T Roarty K Hilsenbeck S Rosen JM. Fibroblast growth factor receptor signaling is essential for normal mammary gland development and stem cell function. Stem Cells. 2013;31(1):178-89; DOI:10.1002/stem.1266.
28. Guerra DM Giometti IC Price CA Andrade PB Castilho AC Machado MF Ripamonte P Papa PC Buratini J Jr. Expression of fibroblast growth factor receptors during development and regression of the bovine corpus luteum. Reprod Fertil Dev. 2008;20(6):659-64; DOI:10.1071/RD07114.
29. Edwards AK van den Heuvel MJ Wessels JM Lamarre J Croy BA Tayade C. Expression of angiogenic basic fibroblast growth factor platelet derived growth factor thrombospondin-1 and their receptors at the porcine maternal-fetal interface. Reprod Biol Endocrinol. 2011;9:5; DOI:10.1186/1477-7827-9-5.
30. Midwood KS Chiquet M Tucker RP Orend G. Tenascin-C at a glance. J Cell Sci. 2016;129(23):4321-4327; DOI:10.1242/jcs.190546.
31. Naik A Al-Yahyaee A Abdullah N Sam JE Al-Zeheimi N Yaish MW Adham SA. Neuropilin-1 promotes the oncogenic Tenascin-C/integrin β3 pathway and modulates chemoresistance in breast cancer cells. BMC Cancer. 2018;18(1):533; DOI:10.1186/s12885-018-4446-y.
32. Mok SC Wong KK Chan RK Lau CC Tsao SW Knapp RC Berkowitz RS. Molecular Cloning of Differentially Expressed Genes in Human Epithelial Ovarian Cancer. Gynecol Oncol. 1994;52(2):247-52; DOI:10.1006/gyno.1994.1040.
33. Hocevar BA Smine A Xu XX Howe PH. The adaptor molecule Disabled-2 links the transforming growth factor β receptors to the Smad pathway. EMBO J. 2001;20(11):2789-801; DOI: 10.1093/emboj/20.11.2789.
34. Rosenbauer F Kallies A Scheller M Knobeloch KP Rock CO Schwieger M Stocking C Horak I. Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion. EMBO J. 2002;21(3):211-20; DOI:10.1093/emboj/21.3.211.
35. Alwosaibai K Abedini A Al-Hujaily EM Tang Y Garson K Collins O Vanderhyden BC. PAX2 maintains the differentiation of mouse oviductal epithelium and inhibits the transition to a stem cell-like state. Oncotarget. 2017;8(44):76881-76897; DOI:10.18632/oncotarget.20173.
36. Bedford FK Ashworth A Enver T Wiedemann LM. HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human. Nucleic Acids Res. 1993;21(5):1245-9.
37. Tian H McKnight SL Russell DW. Endothelial PAS domain protein 1 (EPAS1) a transcription factor selectively expressed in endothelial cells. Genes Dev. 1997;11(1):72-82.
38. Soufi A Jayaraman PS. PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate. Biochem J. 2008;412(3):399-413; DOI:10.1042/BJ20080035.
39. Kershaw RM Siddiqui YH Roberts D Jayaraman PS Gaston K. PRH/HHEX inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Oncogene. 2014;33(49):5592-600; DOI:10.1038/onc.2013.496.
40. Hämäläinen ER Jones TA Sheer D Taskinen K Pihlajaniemi T Kivirikko KI. Molecular cloning of human lysyl oxidase and assignment of the gene to chromosome 5q23.3-31.2. Genomics. 1991;11(3):508-16.
41. Atsawasuwan P Mochida Y Katafuchi M Kaku M Fong KS Csiszar K Yamauchi M. Lysyl Oxidase Binds Transforming Growth Factor-β and Regulates Its Signaling via Amine Oxidase Activity. J Biol Chem. 2008;283(49):34229-40; DOI:10.1074/jbc.M803142200.
42. Kasashima H Yashiro M Kinoshita H Fukuoka T Morisaki T Masuda G Sakurai K Kubo N Ohira M Hirakawa K. Lysyl oxidase is associated with the epithelial mesenchymal transition of gastric cancer cells in hypoxia. Gastric Cancer. 2016;19(2):431-42; DOI:10.1007/s10120-015-0510-3.
43. Ruiz LA Báez-Vega PM Ruiz A Peterse DP Monteiro JB Bracero N Beauchamp P Fazleabas AT Flores I. Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis. Reprod Sci. 2015;22(12):1496-508; DOI:10.1177/1933719115585144.
44. Haraguchi Y Takiguchi M Amaya Y Kawamoto S Matsuda I Mori M. Molecular cloning and nucleotide sequence of cDNA for human liver arginase. Proc Natl Acad Sci U S A. 1987;84(2):412-5.
45. Wei LH Wu G Morris SM Jr Ignarro LJ. Elevated arginase I expression in rat aortic smooth muscle cells increases cell proliferation. Proc Natl Acad Sci U S A. 2001;98(16):9260-4; DOI:10.1073/pnas.161294898.
46. Yu H Yoo PK Aguirre CC Tsoa RW Kern RM Grody WW Cederbaum SD Iyer RK. Widespread Expression of Arginase I in Mouse Tissues: Biochemical and Physiological Implications. J Histochem Cytochem. 2003;51(9):1151-60; DOI:10.1177/002215540305100905.
47. Dickinson RE Hryhorskyj L Tremewan H Hogg K Thomson AA McNeilly AS Duncan WC. Involvement of the SLIT/ROBO pathway in follicle development in the fetal ovary. 2010;139(2):395-407; DOI:10.1530/REP-09-0182.
48. Duncan WC McDonald SE Dickinson RE Shaw JL Lourenco PC Wheelhouse N Lee KF Critchley HO Horne AW. Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube. Mol Hum Reprod. 2010;16(12):950-9; DOI:10.1093/molehr/gaq055.
49. Strickland P Shin GC Plump A Tessier-Lavigne M Hinck L. SLIT2 and netrin 1 act synergistically as adhesive cues to generate tubular bi-layers during ductal morphogenesis. Development. 2006;133(5):823-32; DOI:10.1242/dev.02261.